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Topical chemoprophylaxis with silver sulphadiazine and silver nitrate chlorhexidine creams: emergence of sulphonamide-resistant Gram-negative bacilli

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Abstract

Controlled trials of 0.5% silver nitrate compresses (SN), 1% silver sulphadiazine cream (SSD), and a cream containing 0.5% silver nitrate and 0.2% chlorhexidine digluconate (SNC) showed that all were comparably effective in protecting burns from infection. SN compresses were much less active against miscellaneous Gram-negative bacilli than the other preparations, and the mean morning and evening temperatures and respiration rates in the patients treated with SN compresses were higher then those of patients treated with SSD. Pseudomonas aeruginosa and Proteus spp, though rare in all groups, were less often found in the patients treated with SN compresses. Sulphonamide-resistant Gram-negative bacilli became predominant during the trial of SSD cream on extensive burns and the prophylactic effectiveness of that preparation was thus reduced in the later stages of the trial.

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... Received for publication 15 June 1976 160 burned patients, which showed it to havesomeprophylactic advantages over 0 5 % silver nitrate compresses, also showed that a large proportion of the Enterobacteriaceae in burns became highly resistant to sulphadiazine during the trial; this was associated with a reduced prophylactic effectiveness of silver sulphadiazine cream (Lowbury et al., 1976). ...
... Resistance of Enterobacteriaceae from burns to sulphonamides and other antimicrobial agents MATERIAL AND METHODS Gram-negative bacilli were isolated from burns as described elsewhere (Lowbury et al., 1976). One strain of every coldny type isolated per patient per Drug resistance in relation to use of silver sulphadiazine cream in a burns unit ...
... RESULTS The Figure shows the proportion of strains isolated from burns of five species of Gram-negative bacilli that were resistant to sulphadiazine during a period covering three trials of silver sulphadiazine and a subsequent period of six months when silver sulphadiazine or sulphonamides were not used. These drugs were withdrawn because of the emergence of a very high incidence of sulphonamideresistant Enterobacteria during the trial of silver sulphadiazine on extensive burns (Lowbury et al., 1976). ...
Article
Topical chemoprophylaxis of extensive burns with silver sulphadiazine cream led to a large increase in the proportion of sulphadiazine-resistant Gram-negative bacilli in a burns unit. When all sulphonamide treatment in the ward was stopped; the incidence of sulphonamide-resistant strains fell back to levels similar to those recorded when silver sulphadiazine treatment was introduced. This was associated with a large reduction in the incidence of resistance of certain Gram-negative bacilli (especially Klebstella sp) to several antibiotics. Transferable resistance to sulphadiazine, shown by conjugation experiments with Escherichia coli K12, was found in a majority of the strains of Klebsiella sp tested, and in other species. A pattern of transferable resistance to tetracycline, cephaloridine, chloramphenicol, ampicillin, carbenicillin, and sulphadiazine (T Ce Cl A Ca S) was found in four of the 22 strains of Klebsiella tested, and closely related patterns were transferred by five other strains. These patterns of resistance were commonly found in Klebsiella sp isolated from burns in the period before the withdrawal of sulphonamides from the ward but were found in none of the Klebsiella strains isolated in the first six months after that period. Strains of Acinetobacter and Proteus, in which transferable resistance was not found, showed no appreciable fall or rise in sulphadiazine resistance; there was no fall in resistance of these organisms to tetracycline, cephaloridine, chloramphenicol, ampicillin or carbenicillin on withdrawal of sulphonamides from the ward, but there were substantial falls in resistance of Acinetobacter to kanamycin, gentamicin, trimethoprim, and tetracycline which were probably not caused by the withdrawal of sulphonamides.
... The advent of silver sulfadiazine, created from the combination of silver nitrate and sodium sulfadiazine, allowed for better delivery of silver, allowing Volume 127, Number 1S • Topical Wound Healing Plastic and Reconstructive Surgery • January Supplement 2011 110,111 Since then, silver sulfadiazine gauze has been used widely as an antibiotic in the topical treatment of second-to third-degree burns. Nanocrystalline silver dressings represent further modification in prolongation of silver delivery. ...
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Chronic wounds represent a significant medical burden. Such wounds fail to normally progress through the stages of healing, often complicated by a proinflammatory milieu caused by increased proteinases, hypoxia, and bacterial burden. As a result, several modalities, such as dressings, antimicrobials, growth factors, and human skin substitutes, have been devised in an attempt to correct the chronic wound environment. This review addresses these modalities with a focus on evidence and randomized controlled trials.
... SSD is an established treatment for burns patients, but concern about its efficacy arose when the emergence of sulphadiazine-resistant bacteria was reported in a burns unit in a Birmingham hospital following SSD treatment of patients with extensive burns [70]. Reports of the development of silver resistant strains are rare, but SSD-resistant bacteria have been recovered [71], [72], [73]. ...
Article
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Antiobiotics are potent antimicrobial agents with high specificity. However the relentless emergence of antibiotic-resistant strains of pathogens, together with the retarded discovery of novel antibiotics has led to the need to find alternative treatments. The most frequently used topical antimicrobials in modern wound care practice include iodine and silver containing products. In the past acetic acid, chlorhexidine, honey, hydrogen peroxide, sodium hypochlorite, potassium permanganate and proflavine have been used. Some of these products seem to be making a return, and other alternatives are being investigated. This review attempts to provide insight into the controversy that surrounds the use of topical antimicrobials by describing their respective mechanisms of action, reviewing supporting evidence and outlining perceived limitations.
... S4). According to studies of silver sulfadiazine, a most commonly used topical antibacterial agent for the treatment of burn wounds, the working concentration used on wounds of rabbit and human (1 %)(28) is 100-1600 times to that directly exposed to the microbial pathogens including Staphylococcus aureus, Escherichia coli, etc. (6.2-100 µg/ml) (3). β-Lapachone in the ointment is less effective than affecting cells directly in the medium and has to diffused through out the ointment to stimulate the cells around the wound area. ...
Article
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Impaired wound healing is a serious problem for diabetic patients. Wound healing is a complex process that requires the cooperation of many cell types, including keratinocytes, fibroblasts, endothelial cells, and macrophages. beta-Lapachone, a natural compound extracted from the bark of the lapacho tree (Tabebuia avellanedae), is well known for its antitumor, antiinflammatory, and antineoplastic effects at different concentrations and conditions, but its effects on wound healing have not been studied. The purpose of the present study was to investigate the effects of beta-lapachone on wound healing and its underlying mechanism. In the present study, we demonstrated that a low dose of beta-lapachone enhanced the proliferation in several cells, facilitated the migration of mouse 3T3 fibroblasts and human endothelial EAhy926 cells through different MAPK signaling pathways, and accelerated scrape-wound healing in vitro. Application of ointment with or without beta-lapachone to a punched wound in normal and diabetic (db/db) mice showed that the healing process was faster in beta-lapachone-treated animals than in those treated with vehicle only. In addition, beta-lapachone induced macrophages to release VEGF and EGF, which are beneficial for growth of many cells. Our results showed that beta-lapachone can increase cell proliferation, including keratinocytes, fibroblasts, and endothelial cells, and migration of fibroblasts and endothelial cells and thus accelerate wound healing. Therefore, we suggest that beta-lapachone may have potential for therapeutic use for wound healing.
... In 1968, 1 per cent sulphadiazine cream (Flamazine) was introduced by Fox in the United States and adopted by us for trial. It compared well with silver nitrate compresses and with silver nitrate and chlorhexidine cream: all of these gave good protection against P. aeruginosa and proteus, but silver sulphadiazine was more effective against coliforms (Lowbury et al., 1976). After about six months, however, resistance developed against silver sulphadiazine. ...
... [9][10][11][12][13][14][15] Ag-SD is an organic complex of ionizable silver and sulfadiazine, and the silver ion acts as a bacteriostatic and bactericidal agent. [16][17][18][19][20][21][22][23][24][25][26] We prepared an artificial dermis impregnated with Ag-SD. The objective of this study was to investigate the in vitro Ag-SD release from the artificial dermis and its degradation in phosphate buffer solution (PBS) containing collagenase. ...
Article
This article describes the antibacterial effects of an artificial dermis impregnated with silver sulfadiazine (Ag-SD) in vitro as well as in vivo. In the in vitro test, silver release from the artificial dermis impregnated with Ag-SD, by immersion in collagenase solution was controlled by the degradation of the collagen sponge.The artificial dermis impregnated with 3% or higher doses of Ag-SD completely suppressed the growth of Pseudomonas aeruginosa (Ps.) or Staphylococcus aureus (St.). The cytotoxicity test revealed that impregnation of 5% or higher doses of Ag-SD suppressed the growth of fibroblasts. However, when the artificial dermis impregnated with Ag-SD was implanted into full-thickness skin defects on the backs of guinea pigs, no tissue damage was histologically observed around the implanted site of the dermis. In the in vivo test, the artificial dermis impregnated with 10% Ag-SD, which was grafted on experimentally contaminated wounds in the backs of guinea pigs, macroscopically suppressed degradation of the collagen sponge, and significantly reduced the growth of both Ps. and St., compared with artificial dermis without Ag-SD. We conclude that collagen sponge impregnated with Ag-SD is a promising artificial dermis applicable to treat contaminated wounds. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res 57: 346–356, 2001
... The emergence of SSD-resistant bacteria in a Burns Unit in Birmingham was recorded by Lowbury et al (1976). When the prophylactic effects of SSD were compared to silver nitrate (SN) in severe burns patients, S. aureus was more frequently isolated from wounds treated with SSD, and coliforms were more frequently isolated from SN patients. ...
Article
My first aim is to present the state of burn care during the few years before the Battle of Britain in August-October 1940. This gives the climate of thought in which McIndoe and his collegues faced the challenge of burns. We are inclined to forget the helplessness of surgeons faced with extensive burns at that time. Some of the great changes in burn management in the past 40 years are then described and a claim is made that the results show a real improvement in treatment.
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The inclusion of agar medium containing 0.5 mM AgNO3 in the hospital laboratory replicating system for routine antibiotic-susceptibility determinations resulted in identification of species of Enterobacteriaceae (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Proteus mirabilis, and Citrobacter freundii) with silver resistance. Since the study began in October, 1975, 11 in-hospital patients receiving silver sulfadiazine for burn wound prophylaxis have yielded silver-resistant bacteria from their infected burns. During this treatment routine burn-site cultures from these patients yielded 230 isolates of Enterobacteriaceae, including 211 which were sulfonamide-resistant, 97 of which were also silver-resistant, and 38 of which were untested for silver resistance. Seven silver-resistant but sulfonamide-sensitive isolates were incidentally recovered from respiratory specimens from four nonburn patients with silver tracheostomy tubes, one silver-resistant sulfonamide-sensitive isolate was recovered from a small infected burn on the foot of an Emergency Room patient. Previous treatment of this burn was unknown. Representative AgNO3-resistant E. coli isolates from four patients were serologically untypable. Serotyping of representative isolates of K. pneumoniae showed a diversity of types except from two patients who had been in the same ward at the same time.
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The antibacterial activity of eight antiseptic creams: 1 per cent silver sulphadiazine; 0.2 per cent nitrofurazone; 0.1, 0.5 and 1 per cent chlorhexidine; 2.2 per cent cerium nitrate; 10 per cent povidone iodine; and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were evaluated in vitro. The evaluation included the minimum inhibitory concentration (MIC) against 100 microorganisms isolated from burn patients, the chronology of the bacterial activity against Ps. aeruginosa and Staph. aureus and the penetration strength of the creams through a novel in vitro model contaminated with 17 microorganisms of different species isolated from burn patients. The results revealed that 0.5 per cent or 1 per cent chlorhexidine, 2.2 per cent cerium nitrate, and 1 per cent silver sulphadiazine with 2.2 per cent cerium nitrate were the creams which were effective at the highest dilutions. 0.5 per cent chlorhexidine and 10 per cent povidone iodine had the greater bactericidal activity. Finally, 0.2 per cent nitrofurazone showed greater penetration strength within the eschar model in comparison with the weaker penetration of 0.5 per cent and 1 per cent chlorhexidine and the absence of penetration by the rest of the antibacterial creams.
Article
The results possible today in the treatment of burns may largely be ascribed to progress in plastic surgery in the field of skin grafts. The use of cultured epidermis, as autologous and homologous grafts, has achieved particularly interesting results.1–4The treatment of burns is a complex question, requiring knowledge not only of plastic surgery but also of other disciplines. Intensive care is the first necessity, followed by nutrition, analgesia, measures against infection, and the use of many pharmaceuticals.5–10This article reviews the medical therapy of burns, emphasizing the importance of using varying treatments for the different stages of the disease.
Chapter
Formulation of topical treatmentTopical treatments used in the management of skin disease
Article
Chlorhexidine and sulphadiazine react synergistically against strains of Pseudomonas. Proteus and Staphylococcus, with high factors of synergy. The impermeability of these strains to sulphadiazine is destroyed by low concentrations of chlorhexidine, permitting the accumulation of sulphadiazine which then inhibits protein synthesis. The combination of these drugs is bactericidal.
Article
A clinical trial was devised to determine whether the healing of partial thickness burns was retarded by the use of silver sulphadiazine cream (SSD) compared with simple, non-bacteriocidal dressings. Biopsy-confirmed partial thickness burns of at least 2% confluent area were dressed according to a strict protocol to compare the rate of epithelialisation of the control dressing, tulle gras, with that obtained with the use of silver sulphadiazine. The same comparative dressing regimen was carried out on a series of split thickness graft donor sites. Twenty such donor sites and fifteen burn areas were admitted to the trial. The mean time to healing of SSD-treated burn areas was longer than that for tulle gras; the difference when analysed by paired t-test was statistically significant (p less than 0.05). There was very little difference in the compared healing rates of the donor sites, which implies that SSD does not retard epithelialisation of dermal depth injuries but rather that the delayed healing is a unique response of the partial thickness burn wound to the presence of SSD. A review of the relevant literature is included in the discussion.
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Sont passes en revue differentes infections et leur traitement: pyodermites (impetigo, erysipele, cellulite, folliculite, furonculose, echtyma gangreneux), infection necrosante des tissus mous, morsures et piqures, infections ulceratives, brulures, infections cutanees specifiques, infections bacteriennes dues a des toxines
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The effect of daily treatment with three current topical antibacterial agents and four experimental formulations of chlorhexidine was evaluated after 1 week in rats with full thickness burns. The burn was seeded with 1 x 10(8) colony forming units (CFU) of a strain of P. aeruginosa isolated from the infected wound of a burn patient. Mafenide acetate resulted in the lowest incidence of muscle invasion and yielded the lowest mean eschar and muscle concentrations. Mafenide acetate, gentamicin, and chlorhexidine diphosphanilate (0.5 per cent) had lower mean eschar and muscle concentrations than silver sulphadiazine 1 per cent alone. Addition of chlorhexidine digluconate (0.5 per cent or 1.0 per cent) to silver sulphadiazine reduced mean eschar concentrations but not muscle concentrations compared to silver sulphadiazine alone. All treatments effectively suppressed systemic invasion of lung and blood and prevented death compared with controls. Mafenide acetate, gentamicin sulphate and chlorhexidine disphosphanilate 0.5 per cent were most effective against this patient strain of P. aeruginosa.
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Isolates of 17 strains of epidemic methicillin-resistant Staphylococcus aureus from outbreaks in ten hospitals in the UK were investigated with a variety of techniques both to explore their properties and to type them in order to confirm or refute known or suspected epidemiology. The techniques consisted of a biotyping system, peptidogylcan analysis, testing of antibiotic sensitivity to 21 agents, various phage-typing methods including heat shock, plasmid pattern analysis, and heat cure derivation of plasmid-less isogenic strains. All strains resembled those originally isolated in Australia, being in the possession of a large number of chromosomal resistance factors, pigmentation, ability to produce lipase and large molecular weight plasmids (c.15 Md to c.23 Md) which conferred resistance to gentamicin, propamidine, ethidium bromide, cetrimide and chlorhexidine. Some strains also had a c.3 Md plasmid conferring chloramphenicol resistance and others a c.1 Md cryptic plasmid. A large percentage of the population was resistant to 25 mg/l methicillin at 37 °C, an unusual feature. All the strategies, with the exception of peptidoglycan analysis, contributed to typing of the strains.
Article
A controlled clinical trial was conducted to compare the value of a cream containing 2% phenoxetol and 0.2% chlorhexidine as a prophylactic agent against wound infection in patients with burns affecting up to 15% total body surface area. The acquisition of bacteria was similar in the two treatment groups but the incidence of Staphylococcus aureus in the burns treated with phenoxetol-chlorhexidine cream significantly lower. The incidence of gram-negative bacilli was low in the two treatment groups, and no wound yielded Pseudomonas aeruginosa. Unlike preparations containing silver, phenoxetol-chlorhexidine does not cause electrolyte imbalance or stain materials with which it comes into contact, and it did not produce adverse effects during this trial.
Article
The short-term effects of five topical antibacterial formulations on the microbial flora of 75 varicose ulcers were studied to develop a preparative programme for skin grafting. The flora before treatment was complex including enterobacteria, pseudomonads, streptococci and staphylococci. Chlorhexidine and gentamicin formulations significantly reduced the number of organisms within 48 h but the antibiotic failed to eliminate streptococci.
Article
Patients with fresh full-thickness burn wounds were randomly assigned to receive wound treatment with daily applications of either 1 per cent silver sulfadiazine plus 0.2 per cent chlorhexidine digluconate cream (Silvazine) or 1 per cent silver sulfadiazine (Flamazine). Fifty-four patients treated with Silvazine were comparable to 67 treated with Flamazine with respect to extent and distribution of burn, age and all aspects of wound and associated treatment. Overall incidence of wound bacterial colonization was less in the Silvazine treated patients (65 per cent versus 88 per cent; P = 0.002). With Silvazine, wound colonization by Staphylococcus aureus was less (41 per cent versus 64 per cent; P = 0.01). Clinical wound infection with Staph, aureus developed in one Silvazine treated patient and five Flamazine treated patients (P = 0.16). Colonization by and infection due to all other organisms did not differ in the two groups. The incidence of graft failure was similar with both agents. In future increasing the concentration of chlorhexidine digluconate above 0.2 per cent might produce an improved prophylactic effect against Gram negative bacteria reported by other authors using the combined agent in in vitro and clinical trials. Silvazine was effective in reducing the incidence of Staph. aureus burn wound colonization without fostering supervening opportunistic infection.
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Article
Full-text available
Silver sulfadiazine (SSD), a topical antimicrobial agent, has been widely used for the prophylaxis and treatment of burn infections during the past 30 years. We determined the antimicrobial activity of SSD, alone and in combination with cerium nitrate (CN), gentamicin and amikacin against 130 recent clinical isolates, including multiresistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. The overall activity of SSD was good against all the tested strains and it was particularly high against MRSA (MIC90 100 microg/ml). CN showed no inhibitory effect, even up to 800 microg/ml, on bacterial strains tested. The combination of SSD and CN was as active as SSD alone. In conclusion, SSD has a broad spectrum of activity at concentrations lower than those commonly used in clinical preparations. All strains were inhibited by less then one-fiftieth of the SSD "in use" concentration (10 mg/ml). Our data confirm the efficacy of this topical agent in the prevention and treatment of infections in burns or other surgical wounds and suggest its possible use in clearing staphylococcal carriage as an alternative to mupirocin.
Article
Topical antibacterial treatment is of major importance in the burn patient. Silver sulfadiazine is an effective agent with low toxicity and few side effects. Deposition of silver in tissues, and absorption of sulfadiazine are both minimal. Present and future problems are represented by the emergence of resistant Gram negative bacilli, including Pseudomonas aeruginosa. The development of related metal sulfadiazines to be used against resistant bacteria is on an investigational stage, and clinical trials are few. Silver sulfadiazine may be used in a variety of other conditions than burns.
Chapter
Silver sulfadiazine (AgSD) was synthesized by Lott (1947) and found byFox (1967, 1968a, 1968b, 1973, 1975, 1977b, 1979), Fox et al. (1969a, 1969b, 1970), and others (Stanford et al. 1969; Grossman 1970; Withers 1970; Dickinson 1973; Burke 1973) to be topically effective in the prevention and treatment of burn infections due to Pseudomonas aeruginosa and other microorganisms. Although AgSD is a sulfonamide drug, its mode of action differs from that of other sulfonamides since its antibacterial effectiveness is not reversed by p-aminobenzoic acid (Fox, 1969a). The original concept of Fox was to combine the oligodynamic heavy-metal antimicrobial action of silver ions (Ag+) with the antimicrobial effect of sulfadiazine. When suspended in a 1% water-miscible ointment base, AgSD was effective topically in reducing the development of invasive, early burn wound sepsis (Fox, 1967)
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Article
Background: Pseudomonas aeruginosa, as an etiological agent, has a prominent infection role in serious burned patients. Burned patients usually treated with antiseptic ointments such as silver sulfadiazine (SSD). This study evaluated the effectiveness of 1% SSD and different concentrations of silver nitrate solution (SNS) on resistant isolates of P. aeruginosa. Methods: Three groups of P. aeruginosa isolates were collected consisting of 63 strains from burned patients (group I), 15 strains from burn-hospital environment (group II) and 70 strains from non-burn patients as control group. The Minimum Inhibitory Concentrations (MICs) of SSD and SNS were determined by agar dilution method and their susceptibility to SSD was evaluated by agar well diffusion method. Results: In group I, 60 (95%) strains were resistant to SSD, whereas only 5 of them were resistant to SNS. In group II, eight out of 15 strains were resistant to SSD with MICs similar to group I while they did not show any resistance to SNS (P<0.001). In control group, all strains were sensitive to SSD and SNS (P<0.001) Conclusion: Most of burned patient isolates were resistant to SSD while most of them were sensitive to SNS. In contrast, all the control isolates were sensitive to SSD and SNS. Frequent administrations of SSD ointment in burned patients surely have caused resistant strains to emerge. Cessation of SNS application in clinic or less administration of SSD in non-burn patients did not induce resistance strains.
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Not all wounds heal in a timely fashion at an expected rate. In many cases, this delay in healing occurs because an infection is present. In some cases, the infection manifests as a wound biofilm, with the wound developing a subtle form of inflammation. In such instances, topical treatment with antiseptics is warranted. This article describes when they need to be used
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Article
The effect of a tulle gras dressing medicated with chlorhexidine was shown to reduce significantly the incidence of Staphylococcus aureus in experimental burns made on guinea-pigs. This dressing apparently did not interfere with wound healing.A controlled clinical trial is described which compared the effects of non-medicated tulle gras with tulle gras containing 0.5 per cent chlorhexidine on the incidence of S. aureus and other bacteria in burns treated in an outpatient department. The medicated dressing significantly reduced the incidence of S. aureus in these wounds. A high proportion of antibiotic-resistant staphylococci were isolated from patients in the trial; the value of chlorhexidine in this situation is discussed.
Chapter
The most common aetiological agents involved in skin and wound infections in infants and children are Staphylococcus aureus and Streptococcus pyogenes These frequently manifest as impetigo, furunculosis, cellulitis and wound infections. Other important bacterial pathogens include Haemophilus influenzae which causes cellulitis, and Gram-negative bacteria such as E. coli and Pseudomonas aeruginosa which are responsible for wound infections.
Article
A controlled trial showed that 1 per cent silver sulphadiazine (SSu) cream applied daily (or at intervals of 2 or 3 days) to burns had greater prophylactic value against Pseudomonas aeruginosa than a cream containing 0.4 per cent silver phosphate with 0.2 per cent chlorhexidine gluconate (SPCI). In another controlled trial, SSu cream had greater prophylactic value against Staphylococcus aureus, P. aeruginosa, proteus species and miscellaneous coliform bacilli than a 10 per cent povidone iodine (PVP-I) cream. It was inferred, from the results of an earlier trial, that silver nitrate chlorhexidine (SNCI) cream would be more effective than SPCI cream as a prophylactic agent against P. aeruginosa, apparently because of the greater solubility of silver nitrate; for this reason, SNCI cream was judged to be an appropriate substitute for SSu cream when sulphonamide-resistant Gram-negative bacilli were predominant in the ward.A trial of 10 per cent povidone iodine and 0–5 per cent silver nitrate solutions applied 6 hourly to exposed bums of the face, compared with no topical application, showed that both solutions reduced bacterial colonization of the burns, but there was no significant reduction in colonization by individual pathogens.
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The effect of silver (Ag) on zinc (Zn) and copper (Cu) contents in liver and metallothionein (MT) was examined in dose-response and time course studies. The Zn contents in livers increased in response to Ag injection or during the period after Ag injection, while the Cu content remained un-changed. After Ag injection, 60.1-71.1% of the Zn contents of livers in the dose-response study and 56.0-60.4% of the Zn contents of livers in the time-course study were detected in cytosol, respectively. The distribution profiles of the hepatic cytosol of Ag-injected rats on a Sephadex. G-75 column showed that the amount of the increased Zn was ascribable to MT. There was a close relationship between the Zn contents in the cytosol and MT in the dose-response study or in the time-course study. Our results indicated that in the dose-response and time course studies, approximately 60% of Zn increments in hepatic cytosol was bound to MT.
Chapter
Prescribing topical treatment Formulation of topical treatment Topical treatments used in the management of skin disease References
Article
A tulle gras dressing medicated with I per cent silver sulphadiazine was shown to reduce significantly the incidence of Staphylococcus aureus in experimental burns made on guinea-pigs. It was shown that the local toxicity of silver sulphadiazine was comparable to that of many common antibiotics; the medicated dressing apparently did not interfere with wound healing.In a controlled clinical trial the effects of a non-medicated tulle gras dressing were compared with a tulle gras dressing containing silver sulphadiazine. The use of silver sulphadiazine reduced the incidence of S. aureus and Gram-negative bacilli in burns treated in an outpatient department. A high proportion of antibiotic-resistant staphylococci were isolated from patients in the trial; the value of alternative therapies in this situation is discussed.
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Bacterial resistance to antibiotics is a well-known phenomenon, which has been extensively described. Despite the early optimism in the 1960s that the advent of the antibiotic era would eradicate bacterial diseases, drug resistance in bacteria has increased at an alarming rate, so that bacterial resistance has been described for most if not all available antibiotics. Multidrug resistance in bacteria is indeed a major clinical problem (Hawkey, 2001). This situation is further exacerbated by the slow pace at which new molecules are being produced and by the rapid microbial adaptation to new antimicrobials. Several reasons have been put forward for the emergence of bacterial resistance to antibiotics, among which the overuse and sometimes misuse of antibiotics have been the most important. More recently, biocides (i.e., disinfectants, antiseptics, and preservatives) commonly used in hospital settings and elsewhere, for example, domiciliary and industrial environments, have been implicated in the emergence of antibiotic resistance in bacteria. This has raised concerns in the scientific community (Bloomfield, 2002; Levy, 2000; Russell, 1999a, 2000, 2002a; Russell and Maillard, 2000; Schweizer, 2001) and among institutions (Anon, 1997) and prompted many investigations into the possible linkage between biocide and antibiotic resistance in bacteria. This chapter aims to give a brief description of disinfectant usage, evidence of resistance to these agents with possible linkage between biocide and antibiotic resistance, and the possible role, or not, of disinfectants in selecting for drug resistance.
Article
In a controlled trial, burns of 28 patients dressed with a cream (SNC) containing 0·5 per cent silver nitrate and 0·2 per cent chlorhexidine gluconate, the control series, acquired Pseudomonas aeruginosa less often (9 of 270 swab samplings, 3·3 per cent) than did a comparable series of burns in 33 patients dressed with a cream (CeN) containing 1·74 per cent cerium nitrate (58 of 370 swab samplings, 16 per cent). No bacterial growth or very scanty growth (in liquid medium only) was found in 122 of 270 (45 per cent) swabs from burns in the SNC cream series and in 62 of 370 (17 per cent) swabs from burns in the CeN cream series.
Article
Unlabelled: Silver has been used successfully for decades as an antibacterial agent and has become a standard treatment for burns and bacterial skin infections. Silver-containing creams, particularly silver sulfadiazine (SSD), possess effective activities against bacteria and fungi. However, there is serious concern that silver ions applied to denuded skin might be absorbed in significant amounts, thus introducing the risk of silver deposition, potentially leading to internal organ injury. In view of these facts we compared the percutaneous absorption and the antimicrobial potency of SSD with a new composition, nanoscalic silver (NSAg). In a murine model topical application of NSAg resulted in significantly lower percutaneous absorption and internal organ deposition compared to SSD. Strikingly, antimicrobial activity of NSAg used as a 0.1% formulation was comparable not only with 0.1% SSD against different bacterial strains including methicillin-resistant Staphylococcus aureus, but also against different yeast and dermatophyte species. From the clinical editor: Nanoscale silver (NSAg) was demonstrated to have significantly lower percutaneous absorption and less accumulation in multiple organs when applied to denuded skin. Its antimicrobial activity against MRSA was not only comparable to silver sulfadiazine, but the formulation was also effective against different yeast and dermatophyte species.
Article
AFTER thermal burns local and systemic infection, especially with Pseudomonas aeruginosa , is a major cause of death. The use of soluble sodium sulfonamides in wounds and burns was investigated during World War II, 1 and in studies of extensive burns, 2 topical antibacterial therapy was combined with treatment for the burn wound by using a neutralized mixture of tannic acid and sodium sulfadiazine. Although the results were good, emphasis shifted to the role of sodium salts in systemic therapy in an era of disbelief in the efficacy of local antibacterial therapy. As predicted in 1952 by Meleney, 3 there is now a renaissance of topical antibacterial therapy with the introduction of dilute silver nitrate solutions 4 and mafenide-containing ointments. 5 Both agents are effective in burn wound sepsis, especially that caused by P aeruginosa , but both also produce characteristic fluid and electrolyte alterations. The hypotonic (29.4 millimol/liter) silver nitrate solution
Article
Between 1946 and 1964 mortality experience in a busy burns unit hardly changed. In 1965 routine prophylaxis against Pseudomonas œruginosa infection with 0.5% silver-nitrate solution was introduced, and since then mortality improved considerably. Probability charts, based on probit analysis, for age of patient and percentage body-surface area burned have been reconstructed.
Article
In a controlled trial of three alternative methods for local treatment of severe burns, a significantly lower incidence of bacterial colonisation was recorded in burns treated with local chemoprophylactic agents than in those treated by exposure in warm, dry air. Of the local chemoprophylactic methods, compresses of 0.5% silver-nitrate solution gave better protection in general against bacterial colonisation than 11.2% mafenide ('Sulfamylon') acetate cream with exposure of burns, but infection with Pseudomonas œruginosa occurred about as often in burns treated with silver-nitrate compresses as in those treated with mafenide cream. Miscellaneous coliform bacilli colonised similar proportions of burns in the three treatment groups. The mean of the highest respiration-rates per patient was significantly higher in patients treated by exposure in warm, dry air than in those treated with silver-nitrate compresses. The mean respiration-rate of patients treated with mafenide was slightly higher than that of patients in the silver-nitrate group, and slightly lower than that of patients in the group treated by exposure in warm, dry air; the mean temperature of patients treated with mafenide was slightly lower than that of the patients treated by exposure, but not apparently different from that of patients treated with silver-nitrate compresses. Mortality in each group was slightly, but not significantly, lower than that expected on a probability chart based on findings in the unit during the years 1965-70. Most of the patients treated with mafenide did not complete the course of treatment because of pain; acidosis occurred only in one patient treated with this agent. Side-effects of silver-nitrate treatment were noted in some patients, including low serum-sodium, acidosis, and diarrhœa. A trial of 1% silver-sulphadiazine cream on smaller burns showed that daily reapplication of the cream gave significantly better protection than reapplication every three or four days; the prophylactic effects of this treatment were similar, whether burns were covered with dressings or exposed.
Article
In a series of controlled prophylactic trials of antibacterial creams on burns of less than 30%, a cream containing 0.5% silver nitrate had a significant prophylactic action against Pseudomonas aeruginosa when compared with an inactive control cream (containing penicillin), but no significantly greater prophylaxis was obtained against Ps. aeruginosa by the addition of chlorhexidine gluconate (0.2%) or of gentamicin sulphate (0.1%) to the silver-nitrate cream; gentamicin cream was as active in prophylaxis against Ps. aeruginosa as silver-nitrate/gentamicin cream. Prophylaxis against Proteus spp. followed a similar pattern, but the addition of gentamicin significantly added to the prophylactic value against Proteus spp. of the cream containing silver nitrate. Unlike these organisms, Staphylococcus aureus was not acquired less often by burns treated with silver-nitrate cream than by those treated with penicillin cream; significant prophylactic effects against Staph. aureus were, however, obtained by the addition of gentamicin and (to a smaller degree) of chlorhexidine to the silver-nitrate cream. Both silver nitrate and gentamicin seemed to have a prophylactic effect against miscellaneous gram-negative bacilli, but this did not quite reach statistical significance. The proportion of swabs that yielded no bacterial growth was significantly greater in the series taken from burns treated with silver-nitrate cream (26%) than from those treated with penicillin cream (4.4%), and in the series from burns treated with silver-nitrate/gentamicin and gentamicin creams (62% and 54% respectively) than in the series from burns treated with silver-nitrate cream. There was no significant emergence of gentamicin or silver-nitrate-resistant bacteria in burns during these trials.
Article
46 patients with extensive burns were treated with silver-nitrate compresses, which had been found highly effective in prophylaxis against Pseudomonas aeruginosa (pycoyanea). The expected mortality in these patients was 21 and the observed mortality was 16; separate analyses in children under thirteen years (27) and in adults (19) showed a reduced mortality only in children. Survival-time of adults was sometimes very prolonged. Only 1 patient died with Ps. aeruginosa septicæmia. The use of silver-nitrate compresses and some other improvements in antibacterial prophylaxis was associated with a large reduction in Ps. aeruginosa in burns and in blood-cultures of patients in the unit.
Article
A series of 5358 consecutive swabs from burns were inoculated in duplicate on 0·03 per cent. cetrimide agar and on an agar medium containing 0·02 per cent. cetrimide with 15 μg per ml nalidixic acid. A larger number of swabs yielded Ps. aeruginosa and a smaller number yielded growth of other bacteria on cetrimide-nalidixic acid than on cetrimide agar.
Article
Controlled trials showed that creams containing silver sulphadiazine, silver nitrate with trimethoprim, sulphadiazine with trimethoprim, and silver sulphadiazine with trimethoprim applied to fresh burns had prophylactic effects against bacterial colonization comparable with and in some respects (e.g., activity against Staphylococcus aureus) superior to that of 0.5 per cent silver nitrate cream. Some trimethoprim-resistant staphylococci and Gramnegative bacilli emerged during the trial, and trimethoprim was therefore considered unsuitable for routine prophylactic use. The addition of trimethoprim to silver sulphadiazine did not increase the prophylactic effect of the application, in spite of some in vitro evidence of synergy. No sulphadiazine-resistant organisms were found to emerge, and no obvious toxic or allergic reactions were observed. Silver sulphadiazine cream was well tolerated by patients and considered to be a suitable agent for prophylactic use.Bacteria sensitive to silver nitrate and resistant to sulphadiazine or sensitive to sulphadiazine and relatively resistant to silver nitrate were all sensitive to silver sulphadiazine. From this it was inferred that silver sulphadiazine acts by virtue of both its antimicrobial components. Silver ions were absorbed by bacteria from silver sulphadiazine, as from silver nitrate solution, in nutrient broth.In an interim assessment of a controlled therapeutic trial, silver sulphadiazine cream applied to burns infected with Pseudomonas aeruginosa appeared to have some therapeutic value.
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